Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support

Galyna Bondar, Ryan Togashi, Martin Cadeiras, Joanna Schaenman, Richard K. Cheng, Lindsay Masukawa, Josephine Hai, Tra Mi Bao, Desai Chu, Eleanor Chang, Maral Bakir, Sophie Kupiec-Weglinski, Victoria Groysberg, Tristan Grogan, Joseph Meltzer, Murray Kwon, Maura Rossetti, David Elashoff, Elaine Reed, Pei Pei PingMario C. Deng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers. Methods & design We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership. Results Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88% in Group I and 27% in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93% prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes. Conclusions In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts.

Original languageEnglish (US)
Article numbere0189420
JournalPloS one
Volume12
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

Fingerprint

Recovery of Function
heart failure
mononuclear leukocytes
Transcriptome
Gene expression
Blood Cells
Blood
Heart Failure
Genes
Recovery
gene expression
Surgery
Survival
surgery
genes
Ambulatory Surgical Procedures
Organ Dysfunction Scores
RNA Sequence Analysis
End Stage Liver Disease
International Normalized Ratio

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support. / Bondar, Galyna; Togashi, Ryan; Cadeiras, Martin; Schaenman, Joanna; Cheng, Richard K.; Masukawa, Lindsay; Hai, Josephine; Bao, Tra Mi; Chu, Desai; Chang, Eleanor; Bakir, Maral; Kupiec-Weglinski, Sophie; Groysberg, Victoria; Grogan, Tristan; Meltzer, Joseph; Kwon, Murray; Rossetti, Maura; Elashoff, David; Reed, Elaine; Ping, Pei Pei; Deng, Mario C.

In: PloS one, Vol. 12, No. 12, e0189420, 12.2017.

Research output: Contribution to journalArticle

Bondar, G, Togashi, R, Cadeiras, M, Schaenman, J, Cheng, RK, Masukawa, L, Hai, J, Bao, TM, Chu, D, Chang, E, Bakir, M, Kupiec-Weglinski, S, Groysberg, V, Grogan, T, Meltzer, J, Kwon, M, Rossetti, M, Elashoff, D, Reed, E, Ping, PP & Deng, MC 2017, 'Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support', PloS one, vol. 12, no. 12, e0189420. https://doi.org/10.1371/journal.pone.0189420
Bondar, Galyna ; Togashi, Ryan ; Cadeiras, Martin ; Schaenman, Joanna ; Cheng, Richard K. ; Masukawa, Lindsay ; Hai, Josephine ; Bao, Tra Mi ; Chu, Desai ; Chang, Eleanor ; Bakir, Maral ; Kupiec-Weglinski, Sophie ; Groysberg, Victoria ; Grogan, Tristan ; Meltzer, Joseph ; Kwon, Murray ; Rossetti, Maura ; Elashoff, David ; Reed, Elaine ; Ping, Pei Pei ; Deng, Mario C. / Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support. In: PloS one. 2017 ; Vol. 12, No. 12.
@article{ba591a323aec4c528dbfeabeb8d32d25,
title = "Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support",
abstract = "Background Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers. Methods & design We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership. Results Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88{\%} in Group I and 27{\%} in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93{\%} prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes. Conclusions In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts.",
author = "Galyna Bondar and Ryan Togashi and Martin Cadeiras and Joanna Schaenman and Cheng, {Richard K.} and Lindsay Masukawa and Josephine Hai and Bao, {Tra Mi} and Desai Chu and Eleanor Chang and Maral Bakir and Sophie Kupiec-Weglinski and Victoria Groysberg and Tristan Grogan and Joseph Meltzer and Murray Kwon and Maura Rossetti and David Elashoff and Elaine Reed and Ping, {Pei Pei} and Deng, {Mario C.}",
year = "2017",
month = "12",
doi = "10.1371/journal.pone.0189420",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support

AU - Bondar, Galyna

AU - Togashi, Ryan

AU - Cadeiras, Martin

AU - Schaenman, Joanna

AU - Cheng, Richard K.

AU - Masukawa, Lindsay

AU - Hai, Josephine

AU - Bao, Tra Mi

AU - Chu, Desai

AU - Chang, Eleanor

AU - Bakir, Maral

AU - Kupiec-Weglinski, Sophie

AU - Groysberg, Victoria

AU - Grogan, Tristan

AU - Meltzer, Joseph

AU - Kwon, Murray

AU - Rossetti, Maura

AU - Elashoff, David

AU - Reed, Elaine

AU - Ping, Pei Pei

AU - Deng, Mario C.

PY - 2017/12

Y1 - 2017/12

N2 - Background Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers. Methods & design We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership. Results Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88% in Group I and 27% in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93% prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes. Conclusions In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts.

AB - Background Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers. Methods & design We conducted a study with 29 patients undergoing MCS-surgery in a tertiary academic medical center from 2012 to 2014. PBMC samples were collected one day before surgery (day -1). Clinical data was collected on day -1 and day 8 postoperatively. Patients were classified by Sequential Organ Failure Assessment score and Model of End-stage Liver Disease Except INR score (measured eight days after surgery): Group I = improving (both scores improved from day -1 to day 8, n = 17) and Group II = not improving (either one or both scores did not improve from day -1 to day 8, n = 12). RNA-sequencing was performed on purified mRNA and analyzed using Next Generation Sequencing Strand. Differentially expressed genes (DEGs) were identified by Mann-Whitney test with Benjamini-Hochberg correction. Preoperative DEGs were used to construct a support vector machine algorithm to predict Group I vs. Group II membership. Results Out of 28 MCS-surgery patients alive 8 days postoperatively, one-year survival was 88% in Group I and 27% in Group II. We identified 28 preoperative DEGs between Group I and II, with an average 93% prediction accuracy. Out of 105 DEGs identified preoperatively between year 1 survivors and non-survivors, 12 genes overlapped with the 28 predictive genes. Conclusions In AdHF patients following MCS implantation, preoperative PBMC-GEP predicts early changes in organ function scores and correlates with long-term outcomes. Therefore, gene expression lends itself to outcome prediction and warrants further studies in larger longitudinal cohorts.

UR - http://www.scopus.com/inward/record.url?scp=85038233557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038233557&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0189420

DO - 10.1371/journal.pone.0189420

M3 - Article

C2 - 29236770

AN - SCOPUS:85038233557

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0189420

ER -